Search

Objective Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient’s quality of life. Methods We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated. Results Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function. Conclusions In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function.

To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia.A health insurance claims database and a spontaneous adverse drug reaction database were used.Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years.It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.

Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database.Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal.Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma.mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.

MYB-NFIB and MYBL1-NFIB have been reported in ~60% of adenoid cystic carcinoma cases, but driver alterations in the remaining ~40% of adenoid cystic carcinoma remain unclear. We examined 100 adenoid cystic carcinoma cases for MYB and MYBL1 locus rearrangements by fluorescence in situ hybridization (FISH) with originally designed probe sets using formalin-fixed paraffin-embedded materials. Approximately one-third of samples were also analyzed by fusion transcript-specific RT-PCR and capture RNA sequencing. In the 27 cases with frozen materials, MYB-NFIB and MYBL1-NFIB fusion transcripts were detected in 9 (33%) and 6 cases (22%) by RT-PCR, respectively. Meanwhile, high expression of MYB (18 cases, 67%) or MYBL1 (9 cases, 33%) was detected in all 27 cases in a mutually exclusive manner, regardless of its form (full-length, truncation, or fusion transcript). Interestingly, genomic rearrangements around the corresponding highly-expressed gene were observed in all 27 cases by FISH, suggesting a causative relationship between genomic rearrangements and gene expression. Among the 100 cases, including additional 73 cases, 97 harbored genomic rearrangements in the MYB (73 cases) or MYBL1 locus (24 cases) including 10 cases with atypical FISH patterns undetectable through ordinary split FISH approaches: breakpoints far distant from MYB (5 cases) and a small NFIB locus insertion into the MYB (3 cases) or MYBL1 locus (2 cases). In clinicopathological analyses, histological grade, primary tumor size, and lymph node metastasis were identified as prognostic factors, whereas MYB/MYBL1 rearrangements were not, but were associated with histological grade. In the present study, MYB or MYBL1 locus rearrangement was detected in nearly all adenoid cystic carcinoma cases, and therefore it would be a good diagnostic marker for adenoid cystic carcinoma. However, fusion transcript-specific RT-PCR for MYB-NFIB and MYBL1-NFIB and ordinary split FISH assays for MYB and MYBL1 were less sensitive, and thus detection methods should be judiciously designed because of the diversity of rearrangement modes in adenoid cystic carcinoma.

Salivary duct carcinoma (SDC) constitutes one of the most aggressive cancers in the salivary gland and is associated with a poor prognosis; however, no established systemic therapy options are available. SDC exhibits biological similarity to prostate and breast cancers, therefore anti-hormone therapy and molecular target therapies are available, however with limited beneficial effects. Galanin and galanin receptors (GALRs) are well established as molecular biomarkers to predict the survival rate and risk of recurrence of head and neck squamous cell carcinoma. The present study investigated the clinicopathological features of patients with SDC and the methylation status of their galanin and GALR genes to demonstrate the prognostic value for this disease. The median overall survival (OS) was 37.2 months. T-stage, N-stage, disease stage, tumor size, and preoperative facial paralysis were significantly associated with OS, whereas human epidermal growth factor receptor 2 (HER2) overexpression was not. GALR1 and GALR2 methylation rates in tumor tissues were significantly increased compared with normal tissues with 9.85- and 4.49-fold increase, respectively. p27kip1 and p57kip2 expression significantly inversely correlated with the methylation rate of GALR1 and GALR2. In addition, the observed GALR1 and/or GALR2 methylation rates were significantly correlated with a decrease in OS. These results suggest that GALR1 and GALR2 may serve as potential prognostic factors and therapeutic targets in SDC.

Objective The first revision of “Japanese Clinical Practice Guideline for Head and Neck Cancer” was made in 2013 by the clinical practice guideline committee of Japan Society for Head and Neck Cancer, in response to the revision of the TNM classification. Methods 34 CQs (Clinical Questions) were newly adopted to describe the diagnosis and treatment methods currently considered most appropriate, and offered recommendation grade made by the consensus of the committee. A comprehensive literature search was performed for studies published between 2001 and 2012 using PubMed. Qualified studies were analyzed and the results were evaluated, consolidated and codified by all the committee members. Results Elective neck dissection (ND) does contribute to improvement in survival and should be performed for patients with high-risk tongue cancer. At present, no research has clearly demonstrated the utility of superselective arterial infusion chemotherapy. However, depending on the site and stage of the cancer, combination with radiotherapy may be useful for preserving organ function or improving survival rate. Concurrent CDDP chemotherapy and adjuvant radiotherapy contributes to improvement of survival rate as an adjuvant therapy for advanced squamous cell carcinoma of the head and neck in patients at high risk of recurrence. The anti-EGFR antibody cetuximab (Cmab) has an additive effect with radiotherapy. However, the indication must be carefully considered since this treatment has not been compared with the standard treatment of chemoradiotherapy. Cmab has been shown to have an additive effect with chemotherapy (CDDP/5-FU) in patients with unresectable metastatic or recurrent cancer. Preoperative and postoperative oral care may reduce the risk of postoperative complications such as surgical wound infection and pneumonia in head and neck cancers. Rehabilitation soon after ND for cervical lymph node metastasis is recommended for maintaining and restoring shoulder function. Conclusions In this article, we described most relevant guidelines and CQs for the diagnosis and treatment of head and neck cancer in Japan. These guidelines are not intended to govern therapies that are not shown here, but rather aim to be used as a guide in searching for the most appropriate treatment for individual patient.

Objectives Total pharyngolaryngectomy with free jejunal reconstruction is often performed in patients with hypopharyngeal carcinoma. However, postoperative speechlessness significantly decreases patient quality of life. We investigated whether Provox® insertion could preserve speech after total pharyngolaryngectomy with free jejunal reconstruction. Study Design Retrospective chart review. Methods A total of 130 cases of secondary Provox® insertions after total pharyngolaryngectomy with free jejunal reconstruction were analyzed. Communication outcomes were compared using the Head and Neck Cancer Understandability of Speech Subscale. Outcomes and complications associated with insertion site (jejunal insertion vs. esophageal insertion) and adjuvant irradiation therapy were also evaluated. Results Provox® insertion had favorable communication outcomes in 102 cases (78.4%). Neither the insertion site nor irradiation affected the communication outcome. Complications were observed in 20 cases (15.4%). Local infection was the most common complication. Free jejunal insertion, in which the resection range was enlarged, had a lower complication rate than did esophageal insertion, and its complication rate was unaffected by previous irradiation. For all patients, the hospitalization duration and duration of speechlessness were 13.4 days and 14.6 months, respectively. Patients receiving jejunal insertions had a significantly shorter hospitalization duration than did those receiving esophageal insertions. Unlike Provox®2, Provox®Vega significantly reduced the complication rate to zero. Conclusion For jejunal inserson of a Provox® prosthetic, a sufficient margin can be maintained during total pharyngolaryngectomy and irradiation can be performed, and satisfactory communication outcomes were observed. Provox® insertion after total pharyngolaryngectomy with free jejunal reconstruction should be considered the standard therapy for voice restoration. Level of Evidence 4.

Owing to increased awareness and use of narrow-band imaging, there are more opportunities to treat superficial pharyngeal cancer (SPC). The present study aimed to describe the short- and long-term outcomes of endoscopic resection (ER) for SPC.This study included 166 consecutive SPC in 113 patients treated during 2006 to 2013 at one referral cancer center. In the first period, we treated patients using endoscopic mucosal resection (EMR), in the second period using conventional ESD (cESD) and in the recent period using double-scope ESD (dsESD), which involves a second thin endoscope for assistance to produce traction. Median follow-up period was 30 months.All lesions were diagnosed as squamous cell carcinoma. Complete resection rate of cESD and dsESD procedures was 56.4% and 82.3% (P 0.01), and local recurrence rate was 2.6% and 0.0%, respectively. Procedure duration was significantly shorter for dsESD than for cESD (P 0.05). Four cases of recurrent lymph node (LN) metastasis were observed; however, all patients with LN metastases survived to a 48-month median interval after neck dissection. Risk factors for LN metastasis included subepithelium invasion, tumor thickness1000 μm, droplet infiltration, and lymphovascular invasion. Overall survival rate after 5 years was 79.5%; no patients died of SPC. Cumulative rate of metachronous SPC after 5 years was 46.5%.ER for SPC is a feasible and effective treatment, although metachronous SPC occurred frequently. For the technique of ER, dsESD was effective.

A standard chemotherapy for recurrent/metastatic salivary gland cancers has not been established. Combination chemotherapy of carboplatin and paclitaxel should be evaluated as a treatment option.This study retrospectively reviewed salivary gland cancer patients who received combination chemotherapy of carboplatin and paclitaxel. The differences in objective responses and in the prognoses according to the different pathological diagnoses were evaluated.A total of 38 patients were enrolled in the study; of them, 18 had salivary duct carcinomas (SDCs), nine had adenoid cystic carcinomas (ACCs), and 11 had other pathological diagnoses. Objective responses were observed in 15 (39%) patients. The median progression-free survival (PFS) was 6.5 months, and the median overall survival (OS) was 26.5 months. ACC patients had relatively low response rates (9%), but there were no significant differences in PFS or OS compared to other sub-types. The treatment was well tolerated, with few adverse events.Salivary gland cancer patients showed a moderate clinical response to the combination chemotherapy of carboplatin and paclitaxel. The objective response rates differed according to the pathological diagnoses, but there were no significant differences in prognoses.

Background Renal function influences decisions regarding treatment for patients with oropharyngeal squamous cell carcinoma (SCC). However, the importance of renal function in oropharyngeal SCC has not yet been reported. Methods Four hundred sixty patients with oropharyngeal SCC treated with curative intent between April 2005 and March 2007 in 12 institutions in Japan were analyzed retrospectively. Results Four hundred three patients (87.6%) showed a creatinine clearance (CrCl) ≥50 mL/min and 57 (12.4%) with a CrCl

Objective We aimed to clarify the suitable surgical management around the paratracheal area of patients who undergo total pharyngolaryngectomy based on the pathological results of hypopharyngeal cancer. Methods The study was conducted under a multicenter, retrospective observational design in Japan. We analyzed histopathological paratracheal lymph node metastasis and thyroid invasion, and recurrence around the paratracheal area for 184 patients who underwent initial surgery among 280 participants. Results There were significant differences in the frequency of metastasis to paratracheal lymph nodes as cN advances (P = 0.0344) and cT advances (P = 0.00028). By subsite, the paratracheal lymph node metastasis ratio was 22/130 patients (16.9%) in piriform sinus (PS), 8/32 (25.0%) in PW, 5/22 (22.7%) in PC and 10/17 (58.8%) in cervical esophagus (Ce+). The ratio of cases with bilateral paratracheal metastasis tended to be higher in cN2c, posterior wall (PW) and postcricoid (PC). Invasion to the thyroid was histopathologically confirmed in 16/184 patients (8.7%). Invasion from the primary lesion was in 15 patients. Conclusion This study indicates that it is better for patients with advanced hypopharyngeal cancer at minimum undergo ipsilateral paratracheal lymph node dissection. Tumor subsite of PW, PC or cN2c disease or disease extending to the Ce+ should be treated with bilateral paratracheal neck dissection. In order to more reliably perform paratracheal dissection, there is also an option to resect the thyroid lobe in the range of dissection. Preservation of the thyroid gland can be considered if invasion into the thyroid gland has been clearly ruled out.

Patients with advanced hypopharyngeal or cervical esophageal cancer have a comparatively high risk of also developing thoracic esophageal cancer. Pharyngolaryngectomy with total esophagectomy is highly invasive, and few reports about it exist. We examined the postoperative complications and respective countermeasures and prognoses of patients who underwent pharyngolaryngectomy with total esophagectomy.Case series with chart review.Department of Head and Neck Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan.We examined the postoperative complications and respective countermeasures and prognoses of 40 patients who underwent pharyngolaryngectomy with total esophagectomy in our hospital.Postoperative complications were observed in 23 patients (57.5%) and consisted of 8 groups: tracheal region necrosis in 5 patients; neck abscess formation/wound infection in 5; fistula in 4; tracheostomy suture leakage in 2; ileus in 2; lymphorrhea in 2; pulmonary complications in 2; and other complications, including hemothorax, tracheoinnominate artery fistula, temporary cardiac arrest due to intraoperative mediastinum operation, methicillin-resistant Staphylococcus aureus enteritis, and sepsis, in 1 patient each. A lethal complication-brachiocephalic vein hemorrhage due to tracheostomy suture leakage and hemorrhagic shock due to tracheoinnominate artery fistula-occurred in 2 (5%) patients. The crude 5-year survival rate was 48.6%.Serious postoperative complications were related to tracheostomaplasty. Although pharyngolaryngectomy with total esophagectomy is highly invasive, we believe that our outlined treatment method is the most appropriate for cases of advanced hypopharyngeal or cervical esophageal cancer that also requires concurrent surgery for esophageal cancer.

Background The effectiveness of the combination chemotherapy of weekly paclitaxel and cetuximab has not yet been compared to that of the current standard regimen, EXTREME (combination of 5-fluorouracil, cisplatin and cetuximab). Methods We retrospectively reviewed the clinical records of R/M SCCHN patients who received cetuximab-containing chemotherapy as a first-line therapy; from these, patients receiving a weekly paclitaxel and cetuximab regimen (cohort A) and the EXTREME regimen (cohort B) were extracted. The responses, prognoses and adverse events of these two cohorts were evaluated. Results A total of 86 patients were included (cohort A, 49; cohort B, 36). Patients with histories of platinum-based chemotherapy were more frequently given the cohort A treatment. Though the response rates were similar in the two cohorts (45% in cohort A and 51% in cohort B; p = 0.83), the progression-free survival (PFS) was significantly more favorable in cohort A by the log-rank test (6.0 months vs 5.0 months; p = 0.027). In the Cox-regression hazard analyses, male gender (hazard ratio [HR] = 2.1, p = 0.010), older age (≥ 70 yo) (HR = 5.0, p = 0.018), PS 0 (HR = 2.2, p = 0.027), no history of platinum chemotherapy (HR = 3.2, p = 0.003) and the presence of a tracheostomy (HR = 2.3, p = 0.039) were favorable factors within cohort A. Conclusion In selected R/M SCCHN patients, the combination of weekly paclitaxel and cetuximab could be the better treatment option than the EXTREME regimen.

Ectopic hamartomatous thymoma (EHT) is an extremely rare benign tumor. EHTs are difficult to differentiate from sarcomas, especially synovial sarcomas. We encountered two cases of EHT that were referred from other hospitals because sarcoma was suspected. In these cases, fusion gene detection via polymerase chain reaction or fluorescence in situ hybridization was useful for differentiating EHT from synovial sarcoma. EHT requires accurate diagnosis before surgery to avoid excessive treatment. Both tumor location and the presence of fat inside the tumor are important imaging findings for EHT, and confirmation of spindle cells, epithelial cells, and mature adipose cells in the tumor is an important pathological finding. It is important to exclude synovial sarcoma from the differential diagnosis via fusion gene analysis.

Papillary thyroid carcinoma (PTC) often metastasizes to the central and lateral neck lymph nodes, but rarely affects retropharyngeal nodes (RPN). We retrospectively reviewed 12 patients (three men, nine women) with PTC who underwent dissection of RPN metastases between 1994 and 2012. Mean age at dissection was 65 years (range 23–77). Dissection was performed with the initial surgery for PTC in eight patients, while the remaining four patients underwent dissection as secondary surgery. RPN metastases arose from an ipsilateral primary in nine patients, bilateral in two, and contralateral in one, with primaries located at the superior pole of the thyroid lobe in nine patients. All patients showed simultaneous or previous lymph node metastases in the upper jugular chain. A transcervical approach was applied for RPN dissection in 11 patients, while a transcervical-transparotid approach was applied in the remaining patient. No patients needed mandibulotomy or showed severe complications. Median duration of follow-up after RPN dissection was 48 months (range 3–206). No recurrences in the retropharyngeal space were identified. Two patients died of the disease, one died from other carcinoma, and five survived with distant metastases from PTC. The remaining four patients remain free of the disease as at the time of writing. If lymph node metastases are identified in the upper jugular chain, the possibility of RPN metastases should be checked. Most RPN metastases from PTC can be dissected safely without mandibulotomy. In particular, low-risk patients can expect favorable outcomes.

Background: The current study sought to assess the role of initial neck dissection (ND) for patients with node-positive oropharyngeal squamous cell carcinomas (OPSCC). Methods: The data for 202 patients with previously untreated node-positive OPSCC were gathered from 12 institutions belonging to the Head and Neck Cancer Study Group in the Japan Clinical Oncology Group. These patients were categorized into two groups, consisting of the initial ND group and the wait-and-see group, according to treatment policy. Results: Regional recurrence was observed in 17 of 93 patients undergoing initial ND, whereas, recurrent or persistent diseases were observed in 40 of 109 patients who did not undergo initial ND. The 4-year overall survival rates (OS) for the wait-and-see group and initial ND groups were 74.0% and 78.7%, respectively, and the 4-year regional control rates (RC) for each group were 77.6% and 84.9%. There were no significant differences in either OS or RC (p = 0.3440 and p = 0.2382, respectively). However, for patients with N3 disease, the 4-year OS of the initial ND group (100%) was favorable. For patients with N2a disease, the 4-year RC of the initial ND group was higher than that of the wait-and-see group statistically (100% vs 62.5%, p = 0.0156). Conclusions: The role of initial ND was limited in patients with node-positive OPSCC. The treatment strategy not involving initial ND is considered feasible and acceptable when nodal evaluation after definitive radiotherapy or chemoradiotherapy is applied adequately. However, it is possible that initial ND improves outcomes in patients with resectable large-volume nodal disease. (C) 2014 Elsevier Ltd. All rights reserved.

Background The purpose of this retrospective analysis was to evaluate ocular function and survival rates among treatment modalities in patients with maxillary sinus cancer with orbital invasion. Methods Eighty-seven patients were classified according to the main treatment modality. Ocular function preservation rates and survival rates were evaluated for each therapeutic modality. Results The 5-year overall survival rate for the en bloc resection, conservative surgery, superselective intra-arterial chemotherapy, and radiotherapy (RADPLAT), intravenous chemoradiotherapy (IV-CRT) was 70%, 35%, 49%, and 31%, respectively. The ocular function preservation rate for each group was 15%, 27%, 30%, and 17%, respectively. In the en bloc resection group, there was no significant difference in the 5-year overall survival rate between patients with orbital exenteration and those without orbital exenteration (72% vs 71%; p = .9321). Conclusion The en bloc resection group showed a favorable survival rate but a low preservation rate. Preservation of orbital contents did not reduce the survival rate. © 2014 Wiley Periodicals, Inc. Head Neck 37: 537–542, 2015

While the biological behavior of follicular thyroid carcinoma (FTC) has been studied in great detail using clinical experience, few studies have investigated pre- or intraoperative factors related to the risk of distant metastasis (DM) among patients with FTC. The aim of this study was to analyze the characteristics of FTC with DM.This study retrospectively investigated 102 patients with FTC who underwent surgery between 1988 and 2013. We compared clinicopathological characteristics between FTC with and without DM.Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg) at initial operation (≥1000ng/ml; p0.0001), widely invasive appearance according to macroscopic findings (p0.0001), thick tumor capsule (≥1mm; p0.0001), vascular invasion (p=0.0003), extrathyroidal invasion (p=0.047), and venous tumor embolism (p=0.045) as significant risk factors for DM. Multivariate analysis conducted using pre- and intraoperative factors identified thick tumor capsule (≥1mm), serum Tg at initial operation (≥1000ng/ml), and macroscopically widely invasive appearance as risk factors independently associated with development of DM.Patients with these risk factors should undergo total thyroidectomy and radioactive iodine ablation.

Background We analyzed the effects of local extension sites on survival in patients with locally advanced maxillary sinus cancer. Methods The criteria for inclusion in this study were as follows: (1) previously untreated maxillary sinus cancer; (2) squamous cell carcinoma; (3) T4 disease; and (4) curative-intent treatment. The data for 118 patients were obtained from 28 institutions across Japan and analyzed for overall survival and local control rates by local extension site. Results Sites with a poor prognosis included the cribriform plate, dura, nasopharynx, middle cranial fossa, and cranial nerves other than V2. There was a significant correlation among these sites, except for the cranial nerves. Additionally, the hard palate was the only site that correlated with nodal involvement and showed a poor treatment outcome. Conclusion Even in cases presenting with similar T4 maxillary sinus cancer, treatment should be performed in consideration of the local extension site. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1567–1572, 2014

Anaplastic thyroid carcinoma has a dismal prognosis and lacks an established therapeutic strategy. We have recently conducted chemotherapy with docetaxel and cisplatin as part of multimodal treatment for eight patients with anaplastic thyroid carcinoma. Docetaxel (75 mg/m2) and cisplatin (75 mg/m2) were administered on day 1 every 4 weeks for six courses. This chemotherapy was used as induction therapy in one patient, as therapy for distant metastases in five patients and as postoperative adjuvant therapy in two patients. Three patients showed partial responses and three patients showed stable disease. After excluding the two patients receiving the treatment as adjuvant therapy the response rate was 50 %. Grade 3 or 4 leukocytopenia occurred in seven patients (88 %), but these adverse events were tolerable. Chemotherapy with docetaxel and cisplatin may thus be feasible for anaplastic thyroid carcinoma.

The aim of this study was to compare the therapeutic outcomes of total pharyngolaryngectomy with those of concomitant chemoradiotherapy in advanced hypopharyngeal cancer. This is a retrospective multi-institutional study. The medical records of 979 patients with hypopharyngeal cancer, who were initially treated between 2006 and 2008, were reviewed. In this study, we matched a group of total pharyngolaryngectomy patients with a second group of chemoradiotherapy patients, according to age, gender, subsite, arytenoid fixation, cartilage invasion, and N classification, and analyzed overall survival, disease-specific survival, and locoregional control rates. The matched-pair analysis included 254 patients. The 5-year overall survival, disease-specific survival, and locoregional control rates were 58.5% and 53.5% (P = 0.30), 68.9% and 68.0% (P = 0.80), and 82.2% and 63.6% (P

Esophageal and head and neck (HN) cancers often occur synchronously, this study aimed to clarify the benefits and disadvantages of synchronous and staged operations for double HN/esophagus cancers. We retrospectively reviewed 43 patients with synchronous double cancer of HN and esophagus treated between July 2005 and July 2014, of whom 33 patients underwent synchronous operation (SYN) and 10 underwent staged operations (STG). We compared the short-term outcomes between the groups. Operation time was longer, amount of blood loss was larger, and hospital stay was longer in the SYN group than in each single surgery of the STG group. Incidence of postoperative complications did not differ between the groups. Tracheal necrosis was observed only in the SYN group. One patient died because of postoperative bleeding in the SYN group, whereas no mortality was seen in the STG group. Both the peripheral white blood cell counts and serum CRP levels during postoperative period were significantly higher in the SYN group than each single surgery of STG group. The staged surgery strategy for patients with synchronous esophagus/HN cancers can attenuate surgical stress and thus may increase safety.

Esophageal and head and neck (H&N) cancers often occur synchronously, this study aimed to clarify the benefits and disadvantages of synchronous and staged operations for double H&N/esophagus cancers. We retrospectively reviewed 43 patients with synchronous double cancer of H&N and esophagus treated between July 2005 and July 2014, of whom 33 patients underwent synchronous operation (SYN) and 10 underwent staged operations (STG). We compared the short-term outcomes between the groups. Operation time was longer, amount of blood loss was larger, and hospital stay was longer in the SYN group than in each single surgery of the STG group. Incidence of postoperative complications did not differ between the groups. Tracheal necrosis was observed only in the SYN group. One patient died because of postoperative bleeding in the SYN group, whereas no mortality was seen in the STG group. Both the peripheral white blood cell counts and serum CRP levels during postoperative period were significantly higher in the SYN group than each single surgery of STG group. The staged surgery strategy for patients with synchronous esophagus/H&N cancers can attenuate surgical stress and thus may increase safety.

Anaplastic thyroid cancer is a fatal disease for which no effective therapeutic strategies exist. Lenvatinib, a tyrosine-kinase inhibitor that targets vascular endothelial growth factor receptor, has recently been approved in Japan for the treatment of patients with unresectable thyroid cancer including anaplastic thyroid cancer. Although lenvatinib, like the other tyrosine-kinase inhibitors, sunitinib and sorafenib, might also confer a risk of bleeding, fatal bleeding as a result of lenvatinib treatment for anaplastic thyroid cancer has not been described. A 61-year-old woman presented with a 7-cm mass in the right lobe of the thyroid, lymph node metastases to the neck and multiple lung metastases. Fine needle aspiration revealed that the tumor was anaplastic thyroid cancer. The TNM classification was T4aN1bM1, stage IVC. Shortly after local curative surgery, a tumor recurred in her neck that was treated with lenvatinib (24 mg/day). Nineteen days later, the common carotid artery ruptured and the lenvatinib was stopped. She received the best possible supportive care but died 40 days after stopping the lenvatinib. Autopsy findings showed that the tumor had invaded the adventitia of the common carotid artery at the region of the neck surgery, and an aneurysm had developed. However, the adventitia of the common carotid artery was preserved at the non-dissected area. Lenvatinib might confer risk for fatal bleeding in patients with recurrent anaplastic thyroid cancer after neck surgery, particularly with dissection around the common carotid artery.

The aim of this study is to evaluate the specificity of diagnosing PTC by fine needle aspiration (FNA) cytology. This study retrospectively reviewed the cytopathological reports of 1066 patients that underwent thyroidectomy based on a diagnosis of PTC by FNA between January 1993 and December 2008. This study re-evaluated the cytology and histopathology of the patients that received false positive diagnoses of PTC by FNA. Ten patients (0.9 %) received false positive diagnoses of PTC by FNA. Three patients were overdiagnosed as having PTC by FNA cytology. In contrast, the nuclear features of PTC in the other seven cases were confirmed by the retrospective reviews of the patients’ FNA cytology. Three of the seven patients showed follicular structures in their resection specimens, thus resulting in a diagnosis of either adenomatous goiter or follicular adenoma. However, PTC could not be diagnosed by histopathology in the remaining four patients, even though the histopathology showed the nuclear features of PTC. Most cases of PTC can be easily diagnosed by cytological and morphological atypia with certain limitations. The difficulty in diagnosing PTC by cytology is because the pathological features of PTC also occur in some benign thyroid tumors. Therefore, immunohistochemical or molecular biological approaches must be combined with current cytological diagnostic techniques for the diagnosis of PTC.

In general, with large mesenteric tumors it may be rather difficult to determine whether infiltration into adjacent large vessels occurred. We wish to stress the importance of preparation for microsurgery when a huge lesion appears close to a large artery in preoperative images, based on our experience of successful microscopical reconstruction of a superior mesenteric artery (SMA) and marked improvement of blocked vascular flow to the small intestine during the surgery. We have experienced a case of mesenteric fibromatosis (MF) invading the SMA and vein, contrary to preoperative expectation. The patient underwent extirpation of a MF, 21 cm in size, with reconstruction of the SMA by microsurgery. The sacrificed small intestine was only 80 cm of the distal ileum with the benefit of microscopic anastomosis between the SMA and a major jejunal artery. Preparations for microscopic surgery must be made with resection of large lesions, because involvement of mesenteric large vessels may be expected. It is possible for microsurgery to extend indications for surgical resection of huge mesenteric tumors.

Extrathyroidal invasion is one of the most significant risk factors for patients with papillary thyroid carcinoma (PTC). The purpose of this study was to evaluate a novel definition of extrathyroidal invasion for patients with PTC as a method for predicting a patient’s prognosis. The prospective study was conducted for consecutive 930 patients with primary PTC who received surgery during 1993–2009. We defined only patients who had preoperative recurrent laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of the trachea and/or esophagus as Ex3. Patients with minimal invasion were classified as Ex1, and patients with massive invasion, when we could shave off the tumors, were classified as Ex2. Patients without extrathyroidal invasion were classified as Ex0. Patients classified Ex3 showed significantly shorter disease-free survival (p = 0.03) and disease-specific survival (p = 0.007) than patients classified Ex2. The time to recurrence at resection sites was shorter in patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to death due to distant metastasis of patients classified Ex3 was significantly shorter than that of patients classified Ex2 (p = 0.02). Within the patients classified Ex3, disease-specific survival of patients with invasion to other nearby structures was shorter than that of patients with invasion to only recurrent laryngeal nerve (p = 0.008). The degree and site of invasion is an important prognostic factor for PTC. Our novel classification of extrathyroidal invasion is valuable in predicting the prognosis of PTC.

1980年1月から2010年12月までの30年間にがん研病院頭頸科で一次治療として手術を行った頭頸部原発粘膜悪性黒色腫40例の治療成績を検討した。男女比1：1，年齢は24～79歳（中央値62歳），観察期間は5～174ヶ月（中央値23ヶ月）であった。原発臓器は鼻副鼻腔：28例，口腔：9例，咽頭：3例。TNM分類（AJCC/UICC第7版）ではT3：8例，T4a：23例，T4b：9例でN0：36例，N1：4例，stage III：6例，stage IVA：25例，stage IVB：9例であった。Kaplan-Meier法による5年局所制御率，粗生存率，無再発生存率は70%，43%，29%であった。TNM分類は臨床的な予後とよく相関し，T4b，N1は予後不良であった。原発後方再発の制御が課題と考えられた。後発頸部リンパ節転移も高率にみとめ，頸部郭清が治療成績の維持に一定の効果を認めた。

The carcinogenetic role of human papillomavirus (HPV) in mobile tongue cancer remains unclear because of conflicting results reported in the literature. This disparity is likely to be due to variations in the samples and methods used. Furthermore, despite a tendency for increased prevalence of mobile tongue cancer in young adults, only a few reports specifically in young patients have been published. In the present study on 32 patients, including six in their 20s, we genotyped the prevalence of HPV using a highly sensitive detection tool in fresh-frozen samples from surgical specimens and a novel detection device with electrochemical DNA chip and loop-mediated isothermal amplification. In addition, we confirmed HPV prevalence by in situ hybridization and immunohistochemistry for the p16(INK4a) protein, regarded as a biomarker of HPV-associated cancers. The frequency of 13 genotypes of high-risk HPV was 0/32 (0%), which was further confirmed by in situ hybridization. Overexpression of p16(INK4a) protein was observed in six of the 32 patients (19%), with four (67%) also overexpressing p53. Because there is usually a lack of p53 overexpression in HPV-associated cancer, it is unlikely that p16(INK4a) protein overexpression is correlated with HPV infection. Consequently, it is unlikely that HPV infection plays an important role in mobile tongue carcinogenesis, in particular in young adults. In addition, our data suggest that the overexpression of p16(INK4a) protein is not an appropriate biomarker for HPV association in mobile tongue carcinogenesis.

当科における上顎癌の治療は1960年代後半から佐藤ら1）の三者併用療法をmodifiedした治療法を行い，その成績は1970年から1980年までの症例で5年粗生存率41.8%が得られていた2）。その後，さらなる成績向上を目指しCT，MRIによる画像診断を取り入れ，術前放射線療法の効果に応じた一塊切除を行なう方法に切り替えた。結果，1980年から2008年までの一塊切除136症例では5年粗生存率：62.1%，5年原発巣制御率75.2%が得られた。術前療法の効果では単独照射より動注照射の方が効果的であった。上顎近傍には眼球等の重要臓器があり顔面形態の保存を含めたQOLを考慮したさまざまな治療方法が示されているが，本稿では上顎扁平上皮癌に対する一塊切除法の成績について報告する。

頭頸部癌の治療後にみられる摂食・嚥下障害に対する当科の取り組みを紹介した。嚥下造影検査，嚥下内視鏡検査を行う際には検査時状況画像ならびに嚥下時産生音を同時記録し，記録された患者の姿勢，体格，意識レベル，表情や意欲，摂食運動，発声，呼吸音，嚥下音むせなどの情報を利用することにより摂食・嚥下障害の効率的な臨床的対応を実現している。また摂食・嚥下障害の訓練法ならびに対応法を短期間に確実に習得させるために入院下集中リハビリテーションを行っており，その副次的効果として短期間での摂食レベルの改善を得ている。さらに頭頸部癌術後患者には摂食・嚥下障害の改善のために各種口腔内装置を適用しており，今回は舌接触補助床と下顎復位装置について紹介した。

It can be difficult to distinguish between primary and metastatic squamous cell carcinoma (SCC) in the lung. Surgical specimens were obtained from two groups of patients, 26 lung SCC patients without histories of any other cancer (the definite primary group) and 17 patients who had undergone surgical removal of SCC emerging in the lung after surgery for tongue SCC (the unknown group). From the former, 26 primary lung SCC were obtained. From the latter, 17 lung tumors and 15 primary tumors of the tongue were obtained. Eleven of the 17 lung tumors from the unknown group were metastatic lung SCC. All specimens were immunostained with cytokeratin (CK)5/6, CK7, CAM5.2, CK19 and p63 antibodies. The frequency of CAM5.2 and CK19 expression was significantly higher in the lung SCC of the definite primary group (21 of 26, 81% and 20 of 26, 78%, respectively) than in the metastatic lung SCC (1 of 11, 9% (P < 0.001) and 2 of 11, 18% (P = 0.003), respectively) or primary SCC of the tongue (5 of 15, 33% (P = 0.002) and 2 of 15, 13% (P < 0.001), respectively). CAM5.2 and CK19 are useful for distinguishing between primary SCC of the lung and metastases from tongue cancer.

The aim of this study was to evaluate the efficacy of surgical resection of oral tongue cancer (OTC) pulmonary metastases. Between 1977 and 2003, 23 OTC patients who developed 1-3 pulmonary metastases underwent metastasectomy. There were 14 men and nine women with a median age at the time of first metastasectomy of 56 years. All patients had advanced squamous cell OTC with synchronous or metachronous regional lymph node metastases. The median tumor-free interval after the last OTC treatment was 12 months. Five patients underwent pneumonectomy, three bilobectomy, 13 lobectomy, and two wedge resection. Two patients underwent a second pulmonary metastasectomy. One patient continues to survive, without recurrence 19 years after metastasectomy. Another patient was alive with disease at 24 months after metastasectomy but was lost to follow-up. Twenty-two out of 23 patients developed systemic metastases. The median interval to systemic recurrence after lung resection was 4.1 months, and 21 out of 23 patients died of OTC (median, 9.5 months) after metastasectomy. Most patients who underwent pulmonary metastasectomy died of the disease within two years of metastasectomy. Even for patients with a solitary metastasis, surgical metastasectomy is not a recommended treatment option.